Migraine is a common disease with a worldwide prevalence rate of 8 to 18%. It occurs more frequently in women than in men, and can occur in both children and adults. Symptoms of migraine include not only headaches but also accompanying symptoms such as nausea, vomiting, photosensitivity, hypersensitivity to sound and hypersensitivity to odor, which are obstacles to physical activity. Such migraine-related disorders cause socio-economic losses worldwide and seriously hamper the quality of life (Krymchantowski et al., New and emerging prophylactic agents for migraine, CNS Drugs, 2002; Jackson et al., A comparative effectiveness meta-analysis of drugs for the prophylaxis of migraine headaches, PLOS ONE, 2015).
Although the pathological mechanism of migraine has not been fully understood until now, it is believed that the electrochemical imbalance in the brain due to the excitability of excessive cranial nerve caused by various environmental and intrinsic factors will act as a cause of migraine. The electrochemical imbalance induces cortical spreading depression (CSD) to stimulate the trigeminal nervous system, resulting in inflammation of the nerve periphery and vasodilation of the meninges, which are thought to cause headaches (Noseda et al., Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain. Pain, 2013; Edvinsson et al., Basic mechanisms of migraine and its acute treatment, Pharmacol Ther., 2012).
Drug treatment for migraine is divided into acute abortive treatment (acute phase treatment) and preventive treatment (prophylactic treatment). Acute abortive treatment is used for the purpose of symptom relief at the occurrence of migraine. Drugs used for acute abortive treatment include simple analgesics such as nonsteroidal anti-inflammatory drugs (NSAID) in cases of mild migraine attacks, and the use of migraine specific drugs such as Triptan should be considered in cases where patients do not respond to simple analgesics.
When using drugs for acute abortive treatment, care should be taken to avoid drug overdose. Triptan contracts the cardiovascular system, and thus it is hardly prescribed to patients with cardiovascular disease. Prophylactic treatment is used for the purpose of reducing the frequency of occurrence or the intensity of migraine attacks during the administration of the medication. Prophylactic treatment should be applied in the following cases: when daily life is interrupted by repeated migraine attacks despite acute abortive treatment; when there is a concern about overuse of acute phase drugs due to the occurrence of headaches at the frequency of twice or more a week or frequent headaches; when the patient exhibits severe side effects to acute phase drugs or if the acute phase drug is contraindicated; when the patient prefers prophylactic treatment; when the patient has a long duration of headaches; and when the patient suffers from uncommon migraine, such as hemiplegia migraine, basal type migraine, migraine with persistent aura, or migraine type cerebral infarction (J. L. Jackson et al., A comparative effectiveness meta-analysis of drugs for the prophylaxis of migraine headaches, PLOS ONE, 2015). Valproate has been used to prevent migraine, but it is known to have side effects such as liver damage and congenital malformations.
A variety of drugs have been used for the treatment or prevention of migraine, but there are still limitations in their use due to the lack of satisfactory level of drug response or side effects. Hence, there is still a need for new drugs with improved efficacy and side effects. In particular, in patients with frequent migraine attacks and severe symptoms, it is more necessary to prevent migraine through complete elimination or persistent prevention of additional attack of migraine, rather than to alleviate the occurring symptoms, and it is required to prevent migraine without serious side effects.